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The poor design of clinical trials of statins in oncology may explain their failure – lessons for drug repurposing

Abdullah, MI; Jawad, MJ; Richardson, A; Wolf, ED

The poor design of clinical trials of statins in oncology may explain their failure – lessons for drug repurposing Thumbnail


Authors

MI Abdullah

MJ Jawad

ED Wolf



Abstract

Statins are widely used to treat hypercholesterolaemia. However, by inhibiting the production of mevalonate, they also reduce the production of several isoprenoids that are necessary for the function of small GTPase oncogenes such as Ras. As such, statins offer an attractive way to inhibit an “undruggable” target, suggesting that they may be usefully repurposed to treat cancer. However, despite numerous studies, there is still no consensus whether statins are useful in the oncology arena. Numerous preclinical studies have provided evidence justifying the evaluation of statins in cancer patients. Some retrospective studies of patients taking statins to control cholesterol have identified a reduced risk of cancer mortality. However, prospective clinical studies have mostly not been successful. We believe that this has occurred because many of the prospective clinical trials have been poorly designed. Many of these trials have failed to take into account some or all of the factors identified in preclinical studies that are likely to be necessary for statins to be efficacious. We suggest an improved trial design which takes these factors into account. Importantly, we suggest that the design of clinical trials of drugs which are being considered for repurposing should not assume it is appropriate to use them in the same way as they are used in their original indication. Rather, such trials deserve to be informed by preclinical studies that are comparable to those for any novel drug.

Acceptance Date Jun 15, 2018
Publication Date Sep 1, 2018
Journal Cancer Treatment Reviews
Print ISSN 0305-7372
Publisher Elsevier
Pages 84-89
DOI https://doi.org/10.1016/j.ctrv.2018.06.010
Keywords statins, clinical trial design, drug repurposing
Publisher URL http://doi.org/10.1016/j.ctrv.2018.06.010

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